US5690910A - Method for treating asthma - Google Patents

Method for treating asthma Download PDF

Info

Publication number
US5690910A
US5690910A US08/516,786 US51678695A US5690910A US 5690910 A US5690910 A US 5690910A US 51678695 A US51678695 A US 51678695A US 5690910 A US5690910 A US 5690910A
Authority
US
United States
Prior art keywords
ulmwh
antigen
molecular weight
composition
dose
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
US08/516,786
Other languages
English (en)
Inventor
Tahir Ahmed
Samuel Broder
John K. Whisnant
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Teva Branded Pharmaceutical Products R&D Inc
Original Assignee
Baker Cummins Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Baker Cummins Pharmaceuticals Inc filed Critical Baker Cummins Pharmaceuticals Inc
Assigned to BAKER NORTON PHARMACEUTICALS, INC. reassignment BAKER NORTON PHARMACEUTICALS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: WHISNANT, JOHN K., BRODER, SAMUEL, AHMED, TAHIR
Priority to US08/516,786 priority Critical patent/US5690910A/en
Priority to CZ1998481A priority patent/CZ292134B6/cs
Priority to KR10-1998-0701167A priority patent/KR100451901B1/ko
Priority to SK172-98A priority patent/SK282759B6/sk
Priority to DE69635023T priority patent/DE69635023T2/de
Priority to NZ315275A priority patent/NZ315275A/xx
Priority to PL96324970A priority patent/PL186912B1/pl
Priority to ES96926952T priority patent/ES2244974T3/es
Priority to HU9901614A priority patent/HUP9901614A3/hu
Priority to CA002229060A priority patent/CA2229060A1/en
Priority to AT96926952T priority patent/ATE300938T1/de
Priority to PCT/US1996/013133 priority patent/WO1997006783A1/en
Priority to ZA9606838A priority patent/ZA966838B/xx
Priority to PT96926952T priority patent/PT844869E/pt
Priority to IL12316696A priority patent/IL123166A/en
Priority to AU66945/96A priority patent/AU701691B2/en
Priority to JP50942897A priority patent/JP3263723B2/ja
Priority to DK96926952T priority patent/DK0844869T3/da
Priority to EP96926952A priority patent/EP0844869B1/en
Priority to UA98020876A priority patent/UA62919C2/uk
Priority to ARP960103997A priority patent/AR003271A1/es
Priority to US08/904,565 priority patent/US5980865A/en
Publication of US5690910A publication Critical patent/US5690910A/en
Application granted granted Critical
Priority to MXPA/A/1998/001165A priority patent/MXPA98001165A/es
Priority to HK98106409A priority patent/HK1007060A1/xx
Priority to US09/304,814 priority patent/US6193957B1/en
Priority to NZ337996A priority patent/NZ337996A/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/727—Heparin; Heparan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics

Definitions

  • the invention relates to methods and compositions for preventing and reversing the symptoms and manifestations of asthma.
  • Chronic asthma can be considered to be predominantly an inflammatory disease with associated bronchospasm.
  • the degree of reactivity and narrowing of the bronchi in response to stimuli is greater in asthmatics than in normal individuals. Persistent inflammation is responsible for the bronchial hyperreactivity or airway hyperresponsiveness. Mucosal edema and mucus plugging and hypersecretion may be present; pulmonary parenchyma is normal. Airway narrowing may reverse spontaneously or with therapy.
  • Type 1 (immediate) immune responses may play an important role in the development of asthma in children and many adults; however, when onset of disease occurs in adulthood, allergic factors may be difficult to identify. Exposure to cold dry air, exercise and other aggravating factors also may trigger asthma.
  • Beta agonists are useful as bronchodilator agents; they stimulate beta 2 -adrenergic receptors, increase intracellular cAMP, and may inhibit the release of mast cell mediators.
  • Other useful drugs include theophylline and related xanthine drugs, which produce bronchodilation through unknown mechanisms; the biscromone, cromolyn, which prevents the release of mediator substances and blocks respiratory neuronal reflexes, and corticosteroids, which primarily decrease inflammation and edema.
  • Anticholinergic drugs may relieve bronchospasm by blocking parasympathetic cholinergic impulses at the receptor level.
  • Antihistamines occasionally prevent or abort allergic asthmatic episodes, particularly in children, but they can only be partially effective in asthma because histamine is only one of many mediators.
  • the current drug modalities used for treatment of allergy-induced asthma suffer from a number of drawbacks.
  • the conventional agents have a relatively short duration of action and may be partially or wholly ineffective when administered after antigen challenge occurs.
  • agents such as beta 2 -adrenergic agonists and corticosteroids
  • the therapeutic margin of safety with such agents is relatively narrow and patients using them must be carefully monitored.
  • Bronchial hyperreactivity is a hallmark of asthma and is closely related to underlying airway inflammation. Worsening of asthma and airway inflammation is associated with increase in bronchial hyperreactivity, which can be induced by both antigenic and non-antigenic stimuli.
  • Beta 2 -adrenergic agonists are potent agents for the treatment of bronchospasm, but have no effect on airway inflammation or bronchial hyperreactivity. In fact, chronic use of beta 2 -adrenergic agents alone, by causing down regulation of beta 2 -receptors, may worsen bronchial hyperreactivity.
  • corticosteroids are the only effective agents available which diminish bronchial hyperreactivity. Although inhaled corticosteroids are relatively safe in adult patients with asthma, these agents have tremendous toxicity in children, including adrenal suppression and reduced bone density and growth. Thus, the search for safer and effective agents which diminish bronchial hyperreactivity continues.
  • heparin administered intrabronchially can be an effective inhibitor of bronchospasm and bronchoconstriction and is consequently of value in the prophylaxis of asthma (see, e.g., Ahmed et al., New Eng. J. Med., 329:90-95, 1993; Ahmed, Resp. Drug Deliv., IV:55-63, 1994).
  • low molecular weight heparins e.g., heparins with an average molecular weight of 4,000-5,000 daltons
  • these low-weight heparins also exhibit considerably less anticoagulant activity than commercial heparin, a desirable property when these agents are used in the treatment of asthma (see Ashkin et al., Am. Rev. Resp. Dis., 1993 Intl. Conf. Abstracts, p. A660).
  • Still another object of the present invention is to provide a method and compositions as described above which are highly effective in diminishing specific and non-specific bronchial hyperreactivity, and even when administered after antigen challenge to the patient.
  • the invention resides in a method of treating a patient suffering from antigen-induced asthma through the intrabronchial administration to the patient of a pharmaceutical composition comprising from about 0.05 to about 1.0 mg of ultra-low molecular weight heparins per kilogram of patient body weight in each dose.
  • the administration of these heparins can be on an acute basis following antigen challenge or on a chronic basis to suppress bronchial hyperreactivity.
  • the ultra-low molecular weight heparins used in the present invention have average molecular weights of less than 3,000 daltons and may exhibit a low level of anticoagulant activity or substantially no anticoagulant activity at all.
  • Novel inhalant compositions are also provided in the form of liquid or powdered nebulizer or aerosol compositions containing suitable concentrations of ultra-low molecular weight heparins.
  • FIG. 1 is a bar graph illustrating the effect of pretreatment with inhaled ultra-low molecular weight heparin (CY222) at varying dose levels on antigen-induced acute bronchoconstriction in allergic sheep. Data are shown as antigen-induced mean ⁇ SE % change in SR L , without and after pretreatment with CY222.
  • CY222 inhaled ultra-low molecular weight heparin
  • FIG. 2 is a bar graph illustrating the effect of pretreatment with inhaled low molecular weight heparin (CY216) on antigen-induced acute bronchoconstriction in allergic sheep. Data are shown as antigen-induced mean ⁇ SE % change in SR L , without and after pretreatment with CY216.
  • CY216 inhaled low molecular weight heparin
  • FIG. 3 is a bar graph illustrating the effect of pretreatment with inhaled medium molecular weight heparin (Fragmin) on antigen-induced bronchoconstriction in allergic sheep. Data are shown as antigen-induced mean ⁇ SE % change in SR L , without and after treatment with Fragmin.
  • Fragmin medium molecular weight heparin
  • FIG. 4 is a bar graph illustrating the effect of pretreatment with inhaled ultra-low molecular weight heparin (CY222) on antigen-induced airway hyperresponsiveness in allergic sheep. Data are shown as post-antigen mean ⁇ SE PD 4 , as percentage of baseline, without and after pretreatment with CY222.
  • PD 4 Cumulative provocating dose of carbachol, increasing SR L to 400% above baseline
  • FIG. 5 is a bar graph illustrating the effect of pretreatment with inhaled low molecular weight heparin (CY216) on antigen-induced airway hyperresponsiveness in allergic sheep. Data are shown as post-antigen mean ⁇ SE PD 4 , as percentage of baseline, without and after pretreatment with CY216.
  • FIG. 6 is a bar graph illustrating the effect of pretreatment with inhaled medium molecular weight heparin (Fragmin) on antigen-induced airway hyperresponsiveness in allergic sheep. Data are shown as post-antigen mean ⁇ SE PD 4 , as percentage of baseline, without and after pretreatment with Fragmin.
  • Fragmin medium molecular weight heparin
  • FIG. 7 is a graph illustrating the comparative protective effects of inhaled CY222, CY216 and Fragmin on antigen-induced acute bronchoconstrictor response (ABR) in allergic sheep. Data are shown as post-antigen mean ⁇ SE % protection of antigen-induced ABR. Thick horizontal bars represent ID 50 .
  • FIG. 8 is a graph illustrating the comparative protective effects of inhaled CY222, CY216 and Fragmin on antigen-induced airway hyperresponsiveness (AHR) in allergic sheep. Data are shown as post-antigen mean ⁇ SE % protection of antigen-induced changes in PD 4 .
  • FIG. 9 is a bar graph illustrating the effect of CY222 on antigen-induced airway hyperresponsiveness with CY222 being administered as an aerosol immediately after antigen challenge.
  • FIG. 10 is a bar graph illustrating the effect of commercial heparin on antigen-induced airway hyperresponsiveness with commercial heparin being administered as an aerosol immediately after antigen challenge.
  • FIG. 11 is a bar graph illustrating the effect of Fragmin on antigen-induced airway hyperresponsiveness with Fragmin being administered as an aerosol immediately after antigen challenge.
  • Heparin a sulfated mucopolysaccharide
  • Heparin is synthesized in mast cells as a proteoglycan and is particularly abundant in the lungs of various animals.
  • Heparin is not a specific compound of fixed molecular weight but is actually a heterogenous mixture of variably sulfated polysaccharide chains composed of repeating units of D-glucosamine and either L-iduronic or D-glucuronic acids.
  • the average molecular weight of heparin isolated from animal tissues ranges from about 6,000 to about 30,000 daltons.
  • heparin is known primarily as an anticoagulant. This activity results from heparin's ability to bind to some of the residues of antithrombin III (AT-III), accelerating the neutralization by AT-III of activated clotting factors and preventing the conversion of prothrombin to thrombin. Larger amounts of heparin can inactivate thrombin and earlier clotting factors, preventing conversion of fibrinogen to fibrin.
  • AT-III antithrombin III
  • the anticoagulant activity of heparin is related to the molecular weight of its polysaccharide fragments; low molecular weight components or fragments (for example, fragments having a molecular weight of less than 6,000 daltons) have moderate to low antithrombin and hemorrhagic effects. Similarly, low molecular weight heparins isolated from animal tissue have reduced anticoagulant properties because they consist primarily of the lower molecular weight fragments or fractions.
  • heparin which is generally derived from beef lung or pork intestinal mucosa, has an average molecular weight of about 15,000-17,500 daltons.
  • Heparin has been shown to act as a specific blocker of the IP 3 receptors and inhibits IP 3 mediated calcium release. We have previously suggested that heparin may block IP 3 receptors in mast cells and therefore by interfering with signal transduction may modulate mast cell degranulation and mediator release. In vivo and in vitro studies support this concept and have demonstrated that inhaled heparin can attenuate allergic bronchoconstriction in sheep, prevent exercise induced asthma, as well as inhibit anti IgE induced mast cell histamine release. Inhaled heparin in doses up to 1,000 units/kg has been found to have no effect on partial thromboplastin time (PTT), thus, suggesting a "non-anticoagulant" effect.
  • PTT partial thromboplastin time
  • ultra-low molecular weight heparin (ULMWH) fractions are not only effective inhibitors of airway anaphylaxis, but are highly effective in reducing AHR even when administered after antigen challenge.
  • ULMWH ultra-low molecular weight heparin
  • the present invention constitutes a method of treating a patient suffering from antigen-induced asthma who has been challenged with an asthma-inducing antigen comprising the intrabronchial administration to the patient of a pharmaceutical composition containing about 0.05 to about 1.0 mg of one or more ULMWH fractions per kilogram of patient body weight in each dose of said composition, and preferably from about 0.075 to about 0.75 mg/kg per dose.
  • ULMWH may be defined as heparin fractions having an average molecular weight of 3,000 daltons or less. ULMWH having an average molecular weight of 2,500 daltons or less may be even more effective when used in the method of the invention.
  • Each ULMWH fraction may comprise disaccharides, trisaccharides, tetrasaccharides and/or pentasaccharides, as well as molecules of greater chain length.
  • the invention also comprehends the chronic administration of ULMWH to asthma patients to reduce and suppress AHR.
  • Chronic administration refers to administration of the ULMWH-containing compositions at least once daily for at least ten consecutive days.
  • Chronic administration of a composition containing from about 0.05-1.0 mg/kg per dose, and preferably about 0.075-0.75 mg/kg per dose, can be continued indefinitely to provide AHR-suppressant therapy at least comparable to corticosteroids but substantially without side effects.
  • ULMWH fractions which are active and can be used in the present invention for treating asthmatic patients are all N-sulfated; N-desulfated fractions are ineffective.
  • the inhalant ULMWH compositions used in the present invention may comprise liquid or powdered compositions containing ULMWH and suitable for nebulization and intrabronchial use, or aerosol compositions administered via an aerosol unit dispensing metered doses.
  • Suitable liquid compositions comprise ULMWH in an aqueous, pharmaceutically acceptable inhalant solvent, e.g., isotonic saline or bacteriostatic water.
  • the solutions are administered by means of a pump or squeeze-actuated nebulized spray dispenser, or by any other conventional means for causing or enabling the requisite dosage amount of the liquid composition to be inhaled into the patient's lungs.
  • Suitable powder compositions include, by way of illustration, powdered preparations of heparin thoroughly intermixed with lactose or other inert powders acceptable for intrabronchial administration.
  • the powder compositions can be administered via an aerosol dispenser or encased in a breakable capsule which may be inserted by the patient into a device that punctures the capsule and blows the powder out in a steady stream suitable for inhalation.
  • Aerosol formulations for use in the subject method would typically include fluorinated alkane propellants, surfactants and co-solvents and may be filled into aluminum or other conventional aerosol containers which are then closed by a suitable metering valve and pressurized with propellant.
  • the total concentration of ULMWH fractions in any vehicle suitable for use in accordance with the present invention must be sufficiently high to provide the required dose of about 0.05 to 1.0 mg of ULMWH/kg.
  • concentration of ULMWH in the solution in the case of a patient weighing 75 kg should be approximately 1.0-20.0 mg/ml.
  • the ULMWH compositions described herein provide highly effective treatment for antigen-induced asthma even after antigen challenge has occurred.
  • the ULMWH utilized in this experiment not only has a molecular weight well below 3,000, but in addition about 88% of the heparin chains included in this fraction have molecular weights below 2,500.
  • PD 4 airway responsiveness
  • SR L was measured, before and immediately after challenge, and then hourly for up to 2 hours until SR L had returned to the baseline.
  • the post-challenge PD 4 was then measured.
  • the protocol was repeated at least 14 days later, after pretreatment with aerosolized CY222, CY216, and Fragmin, at doses of 0.31, 0.62, 1.25, 2.5, and 5.0 mg/kg.
  • Pretreatment with aerosolized CY222, CY216, and Fragmin attenuated the antigen-induced AHR in a dose dependent fashion; the minimal effective doses were 0.62 mg/kg, 1.25 mg/kg, and 5.0 mg/kg; respectively.
  • the ULMWH fraction, CY222 was the most potent agent, as shown by significant inhibition of antigen-induced bronchoconstriction and AHR at 0.6 mg/kg dose, while CY216 and Fragmin were ineffective at this dose.
  • the group average values of I.D. 50 of CY222, CY216 and Fragmin against allergic bronchoconsriction were 0.5, 1.3 and 1.8 mg/kg, respectively.
  • the respective group average values of I.D. 50 of CY222, CY216 and Fragmin against AHR were 0.51, 2.5 and 4.7 mg/kg.
  • Example II The same experimental protocol was followed as in Example I, except that (a) the three heparin materials administered to the test animals were CY222, commercial heparin (molecular weight approximately 15,000 daltons) and Fragmin, and (b) the heparins were administered to the animals as an aerosol immediately after antigen challenge.
  • the test data are set forth in Table 7 and graphically illustrated in FIGS. 9-11.
  • inhaled CY222 administered after antigen challenge substantially modified post-antigen AHR, restoring AHR levels in the test subjects to baseline levels or above. This effect was not observed with commercial heparin or Fragmin, wherein no improvement in AHR resulted from post-challenge administration of these heparins.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dispersion Chemistry (AREA)
  • Pulmonology (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
US08/516,786 1995-08-18 1995-08-18 Method for treating asthma Expired - Fee Related US5690910A (en)

Priority Applications (26)

Application Number Priority Date Filing Date Title
US08/516,786 US5690910A (en) 1995-08-18 1995-08-18 Method for treating asthma
IL12316696A IL123166A (en) 1995-08-18 1996-08-13 A pharmaceutical preparation containing sections of heparin N-sulfate with a very low molecular weight for short-term treatment
JP50942897A JP3263723B2 (ja) 1995-08-18 1996-08-13 喘息を治療するための組成物、及び喘息にかかった患者を治療するための気管支内薬物の製造における超低分子量ヘパリンの使用
AU66945/96A AU701691B2 (en) 1995-08-18 1996-08-13 Method and composition for treating asthma
DE69635023T DE69635023T2 (de) 1995-08-18 1996-08-13 Ulmwh (ultra-low-molecular weight heparin) zur behandlung von asthma
KR10-1998-0701167A KR100451901B1 (ko) 1995-08-18 1996-08-13 항원-유도성천식환자치료및기도과민반응을감소,억제시키기위한제약학적조성물
PL96324970A PL186912B1 (pl) 1995-08-18 1996-08-13 Zastosowanie i kompozycja do leczenia astmy
ES96926952T ES2244974T3 (es) 1995-08-18 1996-08-13 Ulmwh (heparina de peso molecular ultrabajo) para tratar asma.
HU9901614A HUP9901614A3 (en) 1995-08-18 1996-08-13 Use of ultra-low molecular weights heparins for preparing pharmaceutical compns. for treting asthma
CA002229060A CA2229060A1 (en) 1995-08-18 1996-08-13 Method and composition for treating asthma
AT96926952T ATE300938T1 (de) 1995-08-18 1996-08-13 Ulmwh (ultra-low-molecular weight heparin) zur behandlung von asthma
PCT/US1996/013133 WO1997006783A1 (en) 1995-08-18 1996-08-13 Method and composition for treating asthma
DK96926952T DK0844869T3 (da) 1995-08-18 1996-08-13 ULMWH (heparin med ultralav molekylvægt) til behandling af astma
PT96926952T PT844869E (pt) 1995-08-18 1996-08-13 Hubpm (heparina de ultra-baixo peso molecular) para tratamento da asma
CZ1998481A CZ292134B6 (cs) 1995-08-18 1996-08-13 Farmaceutický přípravek pro léčbu pacienta trpícího astmatem a použití heparinů o ultranízké molekulové hmotnosti
SK172-98A SK282759B6 (sk) 1995-08-18 1996-08-13 Farmaceutická kompozícia na liečbu astmy
NZ315275A NZ315275A (en) 1995-08-18 1996-08-13 Inhalant composition including ultra low mw heparins (ULMWH) to treat asthma
ZA9606838A ZA966838B (en) 1995-08-18 1996-08-13 Method and composition for treating asthma.
EP96926952A EP0844869B1 (en) 1995-08-18 1996-08-13 Ulmwh (ultra-low-molecular weight heparin) for treating asthma
UA98020876A UA62919C2 (en) 1995-08-18 1996-08-13 Method (variants) and composition for treating asthma
ARP960103997A AR003271A1 (es) 1995-08-18 1996-08-15 Una composicion farmaceutica para el tratamiento del asma inducido por un antigeno y uso de la heparina de peso molecular ultra bajo para la preparación de dicha composicón farmacéutica.
US08/904,565 US5980865A (en) 1995-08-18 1997-08-04 Method for treating late phase allergic reactions and inflammatory diseases
MXPA/A/1998/001165A MXPA98001165A (es) 1995-08-18 1998-02-11 Metodo y composicion para el tratamiento del asma
HK98106409A HK1007060A1 (en) 1995-08-18 1998-06-24 Ulmwh (ultra-low-molecular weight heparin) for treating asthma.
US09/304,814 US6193957B1 (en) 1995-08-18 1999-05-04 Pharmaceutical compositions for treating late phase allergic reactions and inflammatory diseases
NZ337996A NZ337996A (en) 1995-08-18 1999-09-23 Method for treating asthma by administering ultra-low molecular weight heparins (ULMWH) by inhalent

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US08/516,786 US5690910A (en) 1995-08-18 1995-08-18 Method for treating asthma

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US08/904,565 Continuation-In-Part US5980865A (en) 1995-08-18 1997-08-04 Method for treating late phase allergic reactions and inflammatory diseases

Publications (1)

Publication Number Publication Date
US5690910A true US5690910A (en) 1997-11-25

Family

ID=24057086

Family Applications (1)

Application Number Title Priority Date Filing Date
US08/516,786 Expired - Fee Related US5690910A (en) 1995-08-18 1995-08-18 Method for treating asthma

Country Status (22)

Country Link
US (1) US5690910A (es)
EP (1) EP0844869B1 (es)
JP (1) JP3263723B2 (es)
KR (1) KR100451901B1 (es)
AR (1) AR003271A1 (es)
AT (1) ATE300938T1 (es)
AU (1) AU701691B2 (es)
CA (1) CA2229060A1 (es)
CZ (1) CZ292134B6 (es)
DE (1) DE69635023T2 (es)
DK (1) DK0844869T3 (es)
ES (1) ES2244974T3 (es)
HK (1) HK1007060A1 (es)
HU (1) HUP9901614A3 (es)
IL (1) IL123166A (es)
NZ (2) NZ315275A (es)
PL (1) PL186912B1 (es)
PT (1) PT844869E (es)
SK (1) SK282759B6 (es)
UA (1) UA62919C2 (es)
WO (1) WO1997006783A1 (es)
ZA (1) ZA966838B (es)

Cited By (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5980865A (en) * 1995-08-18 1999-11-09 Baker Norton Pharmaceuticals, Inc. Method for treating late phase allergic reactions and inflammatory diseases
WO2001093846A2 (en) * 2000-05-23 2001-12-13 The Trustees Of Columbia University In The City Of New York Method for treating respiratory disorders associated with pulmonary elastic fiber injury comprising the use of clycosaminoglycans
US20040152694A1 (en) * 2003-02-04 2004-08-05 Istvan Kurucz Methods and compositions for treating inflammatory disorders of the airways
WO2006026998A1 (en) 2004-09-10 2006-03-16 Pharmaorigin Aps Methods for treating local tracheal, bronchial or alveolar bleeding or hemoptysis
US20070065373A1 (en) * 2003-09-15 2007-03-22 Vectura Ltd. Mucoactive agents for treating a pulmonary disease
CN100352448C (zh) * 1998-10-30 2007-12-05 Ivax研究公司 用于预防药物耐受性的用途和组合物
US20100298260A1 (en) * 2007-11-02 2010-11-25 Momenta Pharmaceuticals, Inc. Non-anticoagulant polysaccharide compositions
US20100316640A1 (en) * 2007-11-02 2010-12-16 Momenta Pharmaceuticals, Inc. Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization
US20100324276A1 (en) * 2007-11-02 2010-12-23 Momenta Pharmaceuticals, Inc. Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization
US20110136757A1 (en) * 2009-12-03 2011-06-09 Opko Health, Inc. Hypersulfated disaccharide formulations
US8071570B2 (en) 2002-10-10 2011-12-06 Aventis Pharma S.A. Mixtures of polysaccharides derived from heparin, their preparation and pharmaceutical compositions containing them
US8424518B2 (en) 2008-06-13 2013-04-23 Mannkind Corporation Dry powder inhaler and system for drug delivery
US8485180B2 (en) 2008-06-13 2013-07-16 Mannkind Corporation Dry powder drug delivery system
CN103269585A (zh) * 2010-10-29 2013-08-28 Opko健康公司 治疗弹性蛋白酶相关病症的超硫酸化双糖
US9220687B2 (en) 2008-12-29 2015-12-29 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
US9233159B2 (en) 2011-10-24 2016-01-12 Mannkind Corporation Methods and compositions for treating pain
US9241903B2 (en) 2006-02-22 2016-01-26 Mannkind Corporation Method for improving the pharmaceutic properties of microparticles comprising diketopiperazine and an active agent
US9283193B2 (en) 2005-09-14 2016-03-15 Mannkind Corporation Method of drug formulation based on increasing the affinity of crystalline microparticle surfaces for active agents
US9346766B2 (en) 2004-08-20 2016-05-24 Mannkind Corporation Catalysis of diketopiperazine synthesis
US9358352B2 (en) 2008-06-13 2016-06-07 Mannkind Corporation Dry powder drug delivery system and methods
US9364619B2 (en) 2008-06-20 2016-06-14 Mannkind Corporation Interactive apparatus and method for real-time profiling of inhalation efforts
US9364436B2 (en) 2011-06-17 2016-06-14 Mannkind Corporation High capacity diketopiperazine microparticles and methods
US9387256B2 (en) 2010-04-16 2016-07-12 Momenta Pharmaceuticals, Inc. Tissue targeting
US9630930B2 (en) 2009-06-12 2017-04-25 Mannkind Corporation Diketopiperazine microparticles with defined specific surface areas
US9675674B2 (en) 2004-08-23 2017-06-13 Mannkind Corporation Diketopiperazine salts for drug delivery and related methods
US9700690B2 (en) 2002-03-20 2017-07-11 Mannkind Corporation Inhalation apparatus
US9706944B2 (en) 2009-11-03 2017-07-18 Mannkind Corporation Apparatus and method for simulating inhalation efforts
US9802012B2 (en) 2012-07-12 2017-10-31 Mannkind Corporation Dry powder drug delivery system and methods
US9801925B2 (en) 1999-06-29 2017-10-31 Mannkind Corporation Potentiation of glucose elimination
US9925144B2 (en) 2013-07-18 2018-03-27 Mannkind Corporation Heat-stable dry powder pharmaceutical compositions and methods
US9943571B2 (en) 2008-08-11 2018-04-17 Mannkind Corporation Use of ultrarapid acting insulin
US9983108B2 (en) 2009-03-11 2018-05-29 Mannkind Corporation Apparatus, system and method for measuring resistance of an inhaler
US10017585B2 (en) 2010-06-17 2018-07-10 Momenta Pharmaceuticals, Inc. Methods and compositions for promoting hair growth
US10016449B2 (en) 2013-05-28 2018-07-10 Momenta Pharmaceuticals, Inc. Pharmaceutical compositions
US10159644B2 (en) 2012-10-26 2018-12-25 Mannkind Corporation Inhalable vaccine compositions and methods
US10307464B2 (en) 2014-03-28 2019-06-04 Mannkind Corporation Use of ultrarapid acting insulin
US10421729B2 (en) 2013-03-15 2019-09-24 Mannkind Corporation Microcrystalline diketopiperazine compositions and methods
US10561806B2 (en) 2014-10-02 2020-02-18 Mannkind Corporation Mouthpiece cover for an inhaler
US10625034B2 (en) 2011-04-01 2020-04-21 Mannkind Corporation Blister package for pharmaceutical cartridges
US10829509B2 (en) 2016-08-16 2020-11-10 Opko Pharmaceuticals, Llc Pure heptasulfated disaccharides having improved oral bioavailability
US11446127B2 (en) 2013-08-05 2022-09-20 Mannkind Corporation Insufflation apparatus and methods

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7056504B1 (en) 1998-08-27 2006-06-06 Massachusetts Institute Of Technology Rationally designed heparinases derived from heparinase I and II
SI1124563T1 (en) * 1998-10-30 2005-02-28 Ivax Research, Inc. Methods and compositions for the prevention of tolerance to bronchodilators
CA2402160C (en) 2000-03-08 2012-02-14 Massachusetts Institute Of Technology Heparinase iii and uses thereof
WO2002023190A2 (en) 2000-09-12 2002-03-21 Massachusetts Institute Of Technology Methods and products related to low molecular weight heparin
AU2002224408B2 (en) * 2000-10-18 2007-08-23 Massachusetts Institute Of Technology Methods and products related to pulmonary delivery of polysaccharides
RU2528093C2 (ru) * 2010-07-21 2014-09-10 Олег Ильич Эпштейн Фармацевтическая композиция и способ лечения острых и хронических заболевания дыхательной системы и синдрома кашля

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2200771T3 (es) * 1991-06-10 2004-03-16 Schering Corporation Formulaciones en aerosol no clorofluorocarbonadas.
AU3938093A (en) * 1992-04-02 1993-11-08 Baker Norton Pharmaceuticals, Inc. Method and composition for treating antigen-induced and exercise-induced asthma

Non-Patent Citations (18)

* Cited by examiner, † Cited by third party
Title
Ahmed, et al., American Physiol. Soc. , pp. 1492 1498 (1993). *
Ahmed, et al., American Physiol. Soc., pp. 1492-1498 (1993).
Ahmed, et al., American Physiol. Soc., pp. 893 901 (1994). *
Ahmed, et al., American Physiol. Soc., pp. 893-901 (1994).
Ahmed, et al., N. Engl. J. Med. , vol. 329, pp. 90 95 (1993). *
Ahmed, et al., N. Engl. J. Med., vol. 329, pp. 90-95 (1993).
Ahmed, et. al., Am. Rev. Respir. Dis. , vol. 145, pp. 566 570 (1992). *
Ahmed, et. al., Am. Rev. Respir. Dis., vol. 145, pp. 566-570 (1992).
Ahmed, Resp. Drug Delivery IV , pp. 55 63 (1994). *
Ahmed, Resp. Drug Delivery IV, pp. 55-63 (1994).
Ashkin, et al., Am. Rev. Resp. Dis. , vol. 147, No. 4, p. A660 (1993). *
Ashkin, et al., Am. Rev. Resp. Dis., vol. 147, No. 4, p. A660 (1993).
Karnovsky et al., Airwaves and Vascular Remodelling , pp. 45 69 (1994). *
Karnovsky et al., Airwaves and Vascular Remodelling, pp. 45-69 (1994).
Lucio, et al., American Physiol. Soc. , pp. 1093 1101 (1992). *
Lucio, et al., American Physiol. Soc., pp. 1093-1101 (1992).
Page, Lancet , vol. 337, pp. 717 720 (1991). *
Page, Lancet, vol. 337, pp. 717-720 (1991).

Cited By (79)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5980865A (en) * 1995-08-18 1999-11-09 Baker Norton Pharmaceuticals, Inc. Method for treating late phase allergic reactions and inflammatory diseases
US20020086852A1 (en) * 1998-05-14 2002-07-04 Cantor Jerome O. Method for treating respiratory disorders associated with pulmonary elastic fiber injury
CN100352448C (zh) * 1998-10-30 2007-12-05 Ivax研究公司 用于预防药物耐受性的用途和组合物
US9801925B2 (en) 1999-06-29 2017-10-31 Mannkind Corporation Potentiation of glucose elimination
WO2001093846A2 (en) * 2000-05-23 2001-12-13 The Trustees Of Columbia University In The City Of New York Method for treating respiratory disorders associated with pulmonary elastic fiber injury comprising the use of clycosaminoglycans
WO2001093846A3 (en) * 2000-05-23 2002-05-23 Univ Columbia Method for treating respiratory disorders associated with pulmonary elastic fiber injury comprising the use of clycosaminoglycans
US9700690B2 (en) 2002-03-20 2017-07-11 Mannkind Corporation Inhalation apparatus
US8071570B2 (en) 2002-10-10 2011-12-06 Aventis Pharma S.A. Mixtures of polysaccharides derived from heparin, their preparation and pharmaceutical compositions containing them
US20040152694A1 (en) * 2003-02-04 2004-08-05 Istvan Kurucz Methods and compositions for treating inflammatory disorders of the airways
US20070065373A1 (en) * 2003-09-15 2007-03-22 Vectura Ltd. Mucoactive agents for treating a pulmonary disease
US7928089B2 (en) 2003-09-15 2011-04-19 Vectura Limited Mucoactive agents for treating a pulmonary disease
US9796688B2 (en) 2004-08-20 2017-10-24 Mannkind Corporation Catalysis of diketopiperazine synthesis
US9346766B2 (en) 2004-08-20 2016-05-24 Mannkind Corporation Catalysis of diketopiperazine synthesis
US10130685B2 (en) 2004-08-23 2018-11-20 Mannkind Corporation Diketopiperazine salts for drug delivery and related methods
US9675674B2 (en) 2004-08-23 2017-06-13 Mannkind Corporation Diketopiperazine salts for drug delivery and related methods
US20070060517A1 (en) * 2004-09-10 2007-03-15 Lars Heslet Methods for preventing and treating local tracheal, bronchial or alveolar bleeding or hemoptysis
US8431535B2 (en) 2004-09-10 2013-04-30 Hoiberg A/S Methods for treating local tracheal, bronchial or alveolar bleeding or hemoptysis
US7807639B2 (en) 2004-09-10 2010-10-05 Pharmaorigin Asp Methods for preventing and treating local tracheal, bronchial or alveolar bleeding or hemoptysis
US20070258971A1 (en) * 2004-09-10 2007-11-08 Pharmaorgin Aps Methods for Treating Local Tracheal, Bronchial or Alveolar Bleeding or Hemoptysis
WO2006026998A1 (en) 2004-09-10 2006-03-16 Pharmaorigin Aps Methods for treating local tracheal, bronchial or alveolar bleeding or hemoptysis
US9717689B2 (en) 2005-09-14 2017-08-01 Mannkind Corporation Method of drug formulation based on increasing the affinity of crystalline microparticle surfaces for active agents
US9446001B2 (en) 2005-09-14 2016-09-20 Mannkind Corporation Increasing drug affinity for crystalline microparticle surfaces
US10143655B2 (en) 2005-09-14 2018-12-04 Mannkind Corporation Method of drug formulation
US9283193B2 (en) 2005-09-14 2016-03-15 Mannkind Corporation Method of drug formulation based on increasing the affinity of crystalline microparticle surfaces for active agents
US9241903B2 (en) 2006-02-22 2016-01-26 Mannkind Corporation Method for improving the pharmaceutic properties of microparticles comprising diketopiperazine and an active agent
US10130581B2 (en) 2006-02-22 2018-11-20 Mannkind Corporation Method for improving the pharmaceutic properties of microparticles comprising diketopiperazine and an active agent
US8592393B2 (en) 2007-11-02 2013-11-26 Momenta Pharmaceuticals, Inc. Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization
US9358252B2 (en) 2007-11-02 2016-06-07 Momenta Pharmaceuticals, Inc. Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization
US9212233B2 (en) 2007-11-02 2015-12-15 Momenta Pharmaceuticals, Inc. Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization
US20100298260A1 (en) * 2007-11-02 2010-11-25 Momenta Pharmaceuticals, Inc. Non-anticoagulant polysaccharide compositions
US20100316640A1 (en) * 2007-11-02 2010-12-16 Momenta Pharmaceuticals, Inc. Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization
US20100324276A1 (en) * 2007-11-02 2010-12-23 Momenta Pharmaceuticals, Inc. Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization
US8569262B2 (en) 2007-11-02 2013-10-29 Momenta Pharmaceuticals, Inc. Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization
US9351992B2 (en) 2007-11-02 2016-05-31 Momenta Pharmaceuticals, Inc. Non-anticoagulant polysaccharide compositions
US10201672B2 (en) 2008-06-13 2019-02-12 Mannkind Corporation Dry powder inhaler and system for drug delivery
US9339615B2 (en) 2008-06-13 2016-05-17 Mannkind Corporation Dry powder inhaler and system for drug delivery
US9358352B2 (en) 2008-06-13 2016-06-07 Mannkind Corporation Dry powder drug delivery system and methods
US9192675B2 (en) 2008-06-13 2015-11-24 Mankind Corporation Dry powder inhaler and system for drug delivery
US10342938B2 (en) 2008-06-13 2019-07-09 Mannkind Corporation Dry powder drug delivery system
US8499757B2 (en) 2008-06-13 2013-08-06 Mannkind Corporation Dry powder inhaler and system for drug delivery
US8485180B2 (en) 2008-06-13 2013-07-16 Mannkind Corporation Dry powder drug delivery system
US9393372B2 (en) 2008-06-13 2016-07-19 Mannkind Corporation Dry powder drug delivery system
US9446133B2 (en) 2008-06-13 2016-09-20 Mannkind Corporation Dry powder inhaler and system for drug delivery
US8424518B2 (en) 2008-06-13 2013-04-23 Mannkind Corporation Dry powder inhaler and system for drug delivery
US9511198B2 (en) 2008-06-13 2016-12-06 Mannkind Corporation Dry powder inhaler and system for drug delivery
US10751488B2 (en) 2008-06-13 2020-08-25 Mannkind Corporation Dry powder inhaler and system for drug delivery
US9662461B2 (en) 2008-06-13 2017-05-30 Mannkind Corporation Dry powder drug delivery system and methods
US8636001B2 (en) 2008-06-13 2014-01-28 Mannkind Corporation Dry powder inhaler and system for drug delivery
US8912193B2 (en) 2008-06-13 2014-12-16 Mannkind Corporation Dry powder inhaler and system for drug delivery
US9364619B2 (en) 2008-06-20 2016-06-14 Mannkind Corporation Interactive apparatus and method for real-time profiling of inhalation efforts
US10675421B2 (en) 2008-06-20 2020-06-09 Mannkind Corporation Interactive apparatus and method for real-time profiling of inhalation efforts
US9943571B2 (en) 2008-08-11 2018-04-17 Mannkind Corporation Use of ultrarapid acting insulin
US9655850B2 (en) 2008-12-29 2017-05-23 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
US10172850B2 (en) 2008-12-29 2019-01-08 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
US9220687B2 (en) 2008-12-29 2015-12-29 Mannkind Corporation Substituted diketopiperazine analogs for use as drug delivery agents
US9983108B2 (en) 2009-03-11 2018-05-29 Mannkind Corporation Apparatus, system and method for measuring resistance of an inhaler
US9630930B2 (en) 2009-06-12 2017-04-25 Mannkind Corporation Diketopiperazine microparticles with defined specific surface areas
US9706944B2 (en) 2009-11-03 2017-07-18 Mannkind Corporation Apparatus and method for simulating inhalation efforts
US20110136757A1 (en) * 2009-12-03 2011-06-09 Opko Health, Inc. Hypersulfated disaccharide formulations
US8546351B2 (en) 2009-12-03 2013-10-01 Opko Health, Inc. Hypersulfated disaccharide formulations
US9387256B2 (en) 2010-04-16 2016-07-12 Momenta Pharmaceuticals, Inc. Tissue targeting
US10017585B2 (en) 2010-06-17 2018-07-10 Momenta Pharmaceuticals, Inc. Methods and compositions for promoting hair growth
CN103269585B (zh) * 2010-10-29 2016-12-21 Opko健康公司 治疗弹性蛋白酶相关病症的超硫酸化双糖
CN103269585A (zh) * 2010-10-29 2013-08-28 Opko健康公司 治疗弹性蛋白酶相关病症的超硫酸化双糖
US10625034B2 (en) 2011-04-01 2020-04-21 Mannkind Corporation Blister package for pharmaceutical cartridges
US10130709B2 (en) 2011-06-17 2018-11-20 Mannkind Corporation High capacity diketopiperazine microparticles and methods
US9364436B2 (en) 2011-06-17 2016-06-14 Mannkind Corporation High capacity diketopiperazine microparticles and methods
US9233159B2 (en) 2011-10-24 2016-01-12 Mannkind Corporation Methods and compositions for treating pain
US10258664B2 (en) 2011-10-24 2019-04-16 Mannkind Corporation Methods and compositions for treating pain
US9610351B2 (en) 2011-10-24 2017-04-04 Mannkind Corporation Methods and compositions for treating pain
US9802012B2 (en) 2012-07-12 2017-10-31 Mannkind Corporation Dry powder drug delivery system and methods
US10159644B2 (en) 2012-10-26 2018-12-25 Mannkind Corporation Inhalable vaccine compositions and methods
US10421729B2 (en) 2013-03-15 2019-09-24 Mannkind Corporation Microcrystalline diketopiperazine compositions and methods
US10016449B2 (en) 2013-05-28 2018-07-10 Momenta Pharmaceuticals, Inc. Pharmaceutical compositions
US9925144B2 (en) 2013-07-18 2018-03-27 Mannkind Corporation Heat-stable dry powder pharmaceutical compositions and methods
US11446127B2 (en) 2013-08-05 2022-09-20 Mannkind Corporation Insufflation apparatus and methods
US10307464B2 (en) 2014-03-28 2019-06-04 Mannkind Corporation Use of ultrarapid acting insulin
US10561806B2 (en) 2014-10-02 2020-02-18 Mannkind Corporation Mouthpiece cover for an inhaler
US10829509B2 (en) 2016-08-16 2020-11-10 Opko Pharmaceuticals, Llc Pure heptasulfated disaccharides having improved oral bioavailability

Also Published As

Publication number Publication date
CZ292134B6 (cs) 2003-08-13
HUP9901614A3 (en) 2000-04-28
DK0844869T3 (da) 2005-12-12
JPH11511196A (ja) 1999-09-28
ZA966838B (en) 1997-02-19
NZ337996A (en) 2001-04-27
WO1997006783A1 (en) 1997-02-27
IL123166A (en) 2002-07-25
KR19990037688A (ko) 1999-05-25
MX9801165A (es) 1998-07-31
EP0844869B1 (en) 2005-08-03
ATE300938T1 (de) 2005-08-15
UA62919C2 (en) 2004-01-15
DE69635023D1 (de) 2005-09-08
CA2229060A1 (en) 1997-02-27
HUP9901614A2 (hu) 1999-09-28
ES2244974T3 (es) 2005-12-16
EP0844869A4 (en) 2003-04-09
SK282759B6 (sk) 2002-12-03
EP0844869A1 (en) 1998-06-03
AU701691B2 (en) 1999-02-04
SK17298A3 (en) 1998-09-09
HK1007060A1 (en) 1999-04-01
CZ48198A3 (cs) 1998-11-11
NZ315275A (en) 2000-01-28
JP3263723B2 (ja) 2002-03-11
AR003271A1 (es) 1998-07-08
AU6694596A (en) 1997-03-12
DE69635023T2 (de) 2006-05-24
KR100451901B1 (ko) 2005-09-12
IL123166A0 (en) 1998-09-24
PL324970A1 (en) 1998-06-22
PT844869E (pt) 2005-10-31
PL186912B1 (pl) 2004-03-31

Similar Documents

Publication Publication Date Title
US5690910A (en) Method for treating asthma
US5980865A (en) Method for treating late phase allergic reactions and inflammatory diseases
JP4585121B2 (ja) 薬剤療法に対する寛容を予防するための方法と組成物
WO1993019734A1 (en) Method and composition for treating antigen-induced and exercise-induced asthma
ES2258145T3 (es) Disacaridos hipersulfatados y procedimientos para la utilizacion de los mismos en el tratamiento de las inflamaciones.
RU2179445C2 (ru) Способ и композиция для лечения астмы
AU775161B2 (en) Method and compositions for treating late phase allergic reactions and inflammatory diseases
Chin et al. Reversal of bronchial obstruction in children with mild stable asthma by aerosolized furosemide
MXPA98001165A (es) Metodo y composicion para el tratamiento del asma
MXPA00000992A (es) "composiciones para el tratamiento de reacciones alergicas en fase tardia y enfermedades inflamatorias"
CZ2000426A3 (cs) Farmaceutický přípravek k léčení pozdní fáze alergické reakce a zánětlivé nemoci

Legal Events

Date Code Title Description
AS Assignment

Owner name: BAKER NORTON PHARMACEUTICALS, INC., FLORIDA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:AHMED, TAHIR;BRODER, SAMUEL;WHISNANT, JOHN K.;REEL/FRAME:007818/0330;SIGNING DATES FROM 19950815 TO 19950817

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

REMI Maintenance fee reminder mailed
LAPS Lapse for failure to pay maintenance fees
STCH Information on status: patent discontinuation

Free format text: PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362

FP Lapsed due to failure to pay maintenance fee

Effective date: 20011125